CN112689884B - Dynamic ion filter for reducing high abundance ions - Google Patents
Dynamic ion filter for reducing high abundance ions Download PDFInfo
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- CN112689884B CN112689884B CN201980044465.8A CN201980044465A CN112689884B CN 112689884 B CN112689884 B CN 112689884B CN 201980044465 A CN201980044465 A CN 201980044465A CN 112689884 B CN112689884 B CN 112689884B
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Classifications
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/26—Mass spectrometers or separator tubes
- H01J49/34—Dynamic spectrometers
- H01J49/40—Time-of-flight spectrometers
- H01J49/401—Time-of-flight spectrometers characterised by orthogonal acceleration, e.g. focusing or selecting the ions, pusher electrode
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/26—Mass spectrometers or separator tubes
- H01J49/34—Dynamic spectrometers
- H01J49/40—Time-of-flight spectrometers
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J29/00—Details of cathode-ray tubes or of electron-beam tubes of the types covered by group H01J31/00
- H01J29/84—Traps for removing or diverting unwanted particles, e.g. negative ions, fringing electrons; Arrangements for velocity or mass selection
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/06—Electron- or ion-optical arrangements
- H01J49/061—Ion deflecting means, e.g. ion gates
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/26—Mass spectrometers or separator tubes
- H01J49/34—Dynamic spectrometers
- H01J49/42—Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
- H01J49/4205—Device types
- H01J49/421—Mass filters, i.e. deviating unwanted ions without trapping
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
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- H01J49/26—Mass spectrometers or separator tubes
- H01J49/34—Dynamic spectrometers
- H01J49/42—Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
- H01J49/4205—Device types
- H01J49/4245—Electrostatic ion traps
- H01J49/425—Electrostatic ion traps with a logarithmic radial electric potential, e.g. orbitraps
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- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
The invention relates to an apparatus (1) for filtering at least one selected ion (m 1、m3) from an ion beam (2), comprising: a unit (3) for creating an electric field to accelerate ions of the ion beam (2) along a flight path of a predetermined length (d), and a controllable ion optical system (4) demarcating the flight path (d) in one direction and for deflecting the selected ions (m 1、m3) from the flight path (F) of the ion beam (2). The apparatus (1) is further designed to control the ion optical system (4) in dependence on the time of flight (t 1、t3) of the selected ions (m 1、m3) along the flight path (d). The invention also relates to a mass spectrometer (10) having the device (1) according to the invention, and to a method for filtering at least one selected ion (m 1、m3) from an ion beam (2).
Description
Technical Field
The present invention relates to an apparatus for filtering ions having at least one selected ion mass from an ion beam, to a mass spectrometer having an apparatus according to the present invention, and to a method for filtering ions having at least one selected ion mass from an ion beam.
Background
The analysis and/or characterization of samples by mass spectrometry is now widely used in a variety of fields, such as chemistry, in particular pharmaceutical chemistry. Many different types of mass spectrometers are known from the prior art, such as sector mass spectrometers, quadrupole mass spectrometers or time-of-flight mass spectrometers, or also mass spectrometers with inductively coupled plasmas. The modes of operation of the different mass spectrometers have been described in a number of publications and are therefore not explained in detail here.
In a mass spectrometer, the corresponding molecules or atoms to be examined are first converted into the gas phase and ionized. Various methods known per se from the prior art can be used for ionization, such as impact ionization, electron impact ionization, chemical ionization, photoionization, field ionization, so-called fast atom bombardment, matrix-assisted laser desorption ionization or electrospray ionization.
After ionization, the ions pass through an analyzer, also known as a mass selector, where they are separated according to their mass-to-charge ratio m/z. A number of different variations of analyzers can also be used. The different modes of operation are for example based on the application of static or dynamic electric and/or magnetic fields or on different times of flight of different ions.
Finally, ions separated by the analyzer are detected in the detector. In this respect, for example, photomultipliers, secondary electron multipliers, faraday traps, belgium detectors, microchannel plates or channel accelerators are already known from the prior art.
The specific requirements for the mass spectrometers used respectively come from the analysis of complex samples, for example, of body fluid proteomes, in particular serum samples. Such samples have a large dynamic range in terms of ion concentration, which is generally not completely detectable by conventional mass spectrometry. Typically, target molecules, such as cytokines, chemokines or tumor markers, are present in such low concentrations that these molecules cannot be detected at all compared to other molecules. This may lead to only a fraction of the substance, as can be recognized in the more homogeneous cell supernatant, being detectable, especially in the case of clinical samples. Furthermore, since the re-detection rate of low concentration substances is typically very low, the reproducibility of the corresponding mass spectrometry analysis may be low.
Thus, it is desirable to increase the detection probability of low concentration substances in complex samples.
In this regard, so-called tandem mass spectrometry is well known, in which specific ions are excited in a targeted manner for fragmentation. Inspection of the fragmentation pattern allows conclusions to be drawn about the starting product. In this regard, a distinction is made between spatial tandem mass spectrometry, in which two fewer analyzers are coupled one after the other, and temporal tandem mass spectrometry, in which ion traps are used. First, scanning is performed over the entire mass range (MS 1). The ions are then fragmented in the impact chamber, for example using an impact gas. Then, for the decomposition products, scanning (MS 2) is similarly performed, but is performed in a reduced mass range. The term "scanning" is understood herein to mean recording a mass spectrum within a particular mass range.
From the "BoxCar acquisition method enables single-shot proteomics at a depth of 10,000proteins in 100minutes(BoxCar collection method published by Floridan Meier et al, nature Methods, journal 2018 (doi: 10.1038/s 41592-018-0003-5) a complex sample analysis method with improved sensitivity to low concentration substances is known that enables single-shot proteomics studies at a depth of 10000 proteins in 100 minutes. First, a scan is performed over the entire available mass range. The available mass range is then divided into a plurality of sub-ranges and the respective ions having mass within the respective sub-ranges are analyzed sequentially and separately from each other. Furthermore, the number of ions to be analyzed may be limited to a specific sub-range. Therefore, a limit can be imposed on the high strength range with respect to the total filling amount. The achievable sensitivity of a mass spectrometer can be significantly improved by the described method, especially for low concentration ions in complex samples. Disadvantageously, however, a compromise must always be found between the duration of the complete cycle and the achievable sensitivity, since the complete process time is significantly prolonged as the number of sub-ranges increases. At the same time, the number of ions collected from the entire ion beam is reduced.
Disclosure of Invention
The object of the present invention is to further increase the detection possibilities for low concentration substances in complex samples.
The above object is achieved by an apparatus, a mass spectrometer and a method.
The apparatus according to the invention is an apparatus for filtering at least one selected ion from an ion beam. The apparatus includes:
-a unit for generating an electric field to accelerate ions of the ion beam along a flight path of a predetermined length, and
-A controllable ion optical system that routes the flight path in one direction and deflects selected ions from the flight path of the ion beam.
Furthermore, the apparatus is designed to control the ion optical system in dependence on the time of flight of the selected ions along the flight path.
In the unit that creates the electric field for accelerating the ion beam ions, time of flight (TOF) measurement principles are used. Thus, different ions contained in the ion beam are separated based on different times of flight.
The ion optics are then used to prevent specific ions from reaching the detector, or alternatively from reaching an ion trap disposed upstream of the detector where they are collected prior to detection by the detector. For example, the ions may be deflected by an electric and/or magnetic field, in particular a switchable electric and/or magnetic field. For this purpose, the ion optical system is controlled, for example, in a time-dependent manner, in particular dynamically. The ion optical system is arranged in particular in an end region of the flight path. The ion beam is preferably a focused ion beam, wherein the ion optical system is arranged at a position having an optimal focus.
The ion optical system is turned on during at least one time interval when ions having a selected ion mass pass through the ion optical system. The ion optics then deflect the ions along their flight path such that the ions are no longer contained in the ion beam and are no longer collected and/or detected.
According to the present invention, it is contemplated in one aspect to deflect each selected ion having each selected ion mass, charge and/or mass-to-charge ratio from the ion beam. However, it is also contemplated to remove ions having ion masses, charges, and/or mass-to-charge ratios within selected ranges from the ion beam.
The ions selected are in particular ions of high concentration substances, in particular ions in complex samples, which is however not a major concern for the corresponding mass analysis.
Mass spectrometers known in the art generally have only limited capabilities for recording and measuring ions. Thus, the detector or the optional ion trap has a certain saturation. On the other hand, identification of particular ions requires that the number of such ions in the ion beam be minimized. As a result of these two boundary conditions, many low concentration species are below the detection limit or sensitivity limit of the mass spectrometer when analyzed by mass spectrometry and therefore cannot be identified.
The present invention solves the above-described problems by selectively deflecting a particular high concentration material from the ion beam in a targeted manner. Thus, low concentration species are present in greater amounts after passing through the ion optical system and can therefore be identified by mass spectrometry. This constitutes a great improvement in metrology in the field of mass spectrometry, in particular in the field of analysis and medical diagnostics.
In an embodiment, the apparatus according to the invention comprises a detector unit, which is designed to detect and/or determine the mass, charge, mass-to-charge ratio and/or intensity of ions contained in the ion beam.
The detector unit is at least for recording a mass spectrum of the ion beam. In some embodiments of the invention, the detector unit may also be designed to further process the recorded mass spectrum. However, this may also be done by a separate computing unit.
In a further embodiment, the apparatus according to the invention accordingly comprises a calculation unit, which is designed to determine the time of flight, mass, charge, mass-to-charge ratio and/or intensity of ions contained in the ion beam. The intensity is a measure of the number of specific ions. The number of different ions contained in the ion beam may also be determined in addition to or instead of the intensity.
In other embodiments, the detector unit may also be part of a mass spectrometer, in particular an existing mass spectrometer, with which the apparatus according to the invention may be used, or which is an integral part of the mass spectrometer. The calculation unit may also be part of a detector unit or may also be part of a mass spectrometer with which the device according to the invention may be used or which is an integral part of the mass spectrometer.
In a further embodiment, the apparatus according to the invention comprises a control unit, which is designed to control the ion optical system in dependence on the time of flight of the selected ions along the flight path. For this purpose, the control unit may interact directly or indirectly with the computing unit and/or the detector unit and/or have, for example, a further separate computing unit. The selected ions may be used to generate a filter pattern based on which the ion optics may be controlled.
The selected ions are preferably determined based on at least one predetermined criterion. For example, in each case, the ions to be deflected may be selected on the basis of the respective intensities, or on the basis of their numbers, or on the basis of their masses and/or charges, in particular on the basis of their mass-to-charge ratios. It is also possible to envisage a specified list (exclusion list) with ions which are not considered for the corresponding analysis. It is also conceivable to select ions based on the complete spectrum of the ion beam.
If a computing unit and a control unit are present, it is conceivable to implement them, for example, in a single electronic unit. However, it is also conceivable to have the computing unit as part of the first electronic unit and the control unit as part of the second electronic unit. Particularly when the detector unit is part of a mass spectrometer, separate electronic units are used for the detector unit and the control unit.
A particularly preferred embodiment of the apparatus includes that the ion optical system comprises at least one Bradbury-Nielson gate. The so-called bradery-nielsen gate comprises a fine-mesh-like arrangement of wire mesh or slats by which a plurality of parallel electromagnetic fields can be generated to deflect ions from the ion beam. Such electromagnetic fields advantageously deflect ions from their respective flight paths only in a small region but with high efficiency. Thus, the brabender-nielsen gate is characterized by minimal impact on the spatial field and thus higher spatial resolution. Furthermore, it is a very fast and precisely switchable or controllable ion optical system.
In another embodiment, the apparatus includes an ion trap for accumulating or depleting at least one predetermined ion or a plurality of predetermined ions within at least one predetermined range. This range is in particular a predetermined range of predetermined ions with respect to mass, charge or mass to charge ratio. This measure allows the sensitivity of the mass spectrometer to be increased even further, which is particularly advantageous in cases where the ion concentration is particularly low. The ion trap is preferably arranged downstream of the ion optical system and upstream of the detector.
Advantageously, the ion trap is an orbitrap or a C-trap.
In one embodiment, the apparatus includes an ion optical system for directing an ion beam at least at a predetermined point in time such that the ion beam passes through the apparatus. However, by means of the ion optical system, the ion beam can on the other hand also be supplied directly to the detector or to an optionally present ion trap. In this case, it is possible, for example, to record mass spectra over the entire usable mass range without being affected by the filtering according to the invention. However, at least one predetermined point in time or during a predetermined time interval, the ion beam may also be directed by suitably controlling the ion optics such that the ion beam passes through the apparatus and at least one selected ion is deflected accordingly before the remaining ion beam is supplied to the detector. The ion optical system preferably comprises at least one ion mirror as described, for example, in document US6614021B1 or US9048078B 2.
Furthermore, the object according to the invention is achieved by a mass spectrometer having a device according to the invention according to at least one of the embodiments. For example, the apparatus can be implemented in a stationary manner in an existing mass spectrometer.
Advantageously, the mass spectrometer has means for generating an ion beam, in particular a focused ion beam, and wherein the apparatus is arranged between the means for generating an ion beam and the detector. For this embodiment, the device is an integral part of the mass spectrometer or permanently mounted in the corresponding mass spectrometer. Depending on the mass spectrometer used, the detector and/or the calculation unit may also be part of the mass spectrometer. In the case of a time-of-flight mass spectrometer, the means for creating an electric field to accelerate ions of the ion beam along a flight path of a predetermined length may also be part of the mass spectrometer. In order to implement the apparatus according to the invention, components that are already part of a mass spectrometer may not need to be duplicated for performing the filtering according to the invention and for performing mass spectrometry.
Similarly, the object according to the invention is achieved by a method for filtering at least one selected ion from an ion beam, in particular by an apparatus according to the invention, and comprising the following method steps:
Accelerating ions of the ion beam along a flight path of a predetermined length, and
-Deflecting selected ions from the flight path of the ion beam according to their flight time along the flight path.
The time of flight of the ions may be determined, for example, based on the mass and/or mass-to-charge ratio of the ions contained in the ion beam. The mass and/or mass-to-charge ratio of the sample to be detected is determined, for example, on the basis of at least one mass spectrum of the sample to be detected in each case, for example together with the charge and/or intensity of the ions contained in the ion beam. The deflection of the selected ions from the path of flight of the ion beam is based on their time of flight along the path of flight, for example by a controllable ion optical system.
In one embodiment of the method, the selected ions are determined based on at least one mass spectrum of the ion beam and/or based on mass, charge, mass to charge ratio and/or intensity of ions contained in the ion beam. The corresponding mass spectrum is in particular a scan over the entire usable mass range, which is established, for example, in advance or during operation of the device at predetermined time intervals. However, the selected ions may also be determined based on at least one mass spectrum of the ion beam that has been filtered at least once.
Instead of or in addition to the spectrum, a list of selected ions may be specified, for example, when it is known which ions are to be filtered. Such a list may be specified once or dynamically generated at predetermined time intervals during operation of the device. Alternatively, other criteria may be used to determine the selected ions, particularly criteria related to mass, charge, mass to charge ratio, retention time, intensity, or variables derived from one or more such variables.
In a preferred embodiment of the method according to the invention, at least one ion is selected whose intensity or number exceeds a predetermined limit value. Thus, ions of a particular predetermined concentration are selected from the respective species in the respective sample and deflected. In each case, this selection of ions to be filtered can advantageously be made in an at least partially automated manner.
One embodiment of the method includes accumulating or depleting at least one predetermined ion or a plurality of predetermined ions within a predetermined range. The accumulated or consumed ions can then be analyzed by mass spectrometry. Advantageously, selected ions that have been filtered or deflected are not accumulated or consumed.
In this respect, it is advantageous to determine the accumulation factor or the consumption factor. Accumulation or depletion occurs in ion traps of known capacity. The input current of ions is also known. If the known amount of applied filtering is additionally determined based on a comparison of the recorded mass spectra before and after filtering is performed, the amount of ions reaching the ion trap may be determined and may also be correspondingly predefined.
It is therefore advantageous to accumulate or consume at least one predetermined ion or a plurality of predetermined ions within a predetermined range with a predetermined accumulation factor or a predetermined consumption factor. By accumulating or depleting at a predetermined accumulation factor or a predetermined depletion factor, the proportion of the respective ion to be accumulated or depleted in the ion beam may advantageously be defined for the respective ion.
In summary, the present invention advantageously makes it possible to precisely and selectively deflect at least one selected ion from the ion beam and thereby filter it. However, ions may also be filtered in parallel, for example, based on their mass, charge, mass-to-charge ratio, and/or intensity, or based on a selected range of these variables. In this way, the sensitivity of the mass spectrometer to low dose substances can be significantly improved. In addition to analyzing complex samples, the invention may also be used in connection with so-called molecular sorting, for example to filter out specific ions from a mixture. Furthermore, another possible application area of the invention is in the field of so-called Data Independent Acquisition (DIA) or in the field of so-called full ion fragmentation. In this case, it is possible to analyze not only the specific mass range in sequence. Instead, the invention allows for the removal or selection and/or addition of molecular modes and/or molecular classes from the entire mass range, in particular by means of a specifically adapted filter mode for filtering the respective ions. For example, the selection may be made with respect to the charge and/or intensity of the ions. It should be noted that the embodiments described in connection with the apparatus according to the invention may also be compared to a mass spectrometer according to the invention and/or a method according to the invention and vice versa.
Drawings
The invention will now be explained in more detail with reference to the following figures. Like elements in the drawings are provided with like reference numerals. In the accompanying drawings:
FIG. 1 is a first illustrative embodiment of an apparatus according to the present invention;
fig. 2 is a second embodiment of an apparatus according to the invention having an ion trap;
Fig. 3 is a third embodiment of an apparatus according to the invention with an ion optical system;
FIG. 4 is a first embodiment of a mass spectrometer according to the invention with an apparatus according to the invention;
FIG. 5 is an embodiment of a mass spectrometer according to the invention with an apparatus according to the invention, wherein the apparatus is an integral part of the mass spectrometer;
Fig. 6 is a mass spectrum over the entire mass range of the mass spectrometer before (a) and after (b to d) filtering selected ions from the respective ion beams.
Detailed Description
Fig. 1 shows a schematic illustration of an apparatus 1 according to the invention for filtering selected ions (here based on selected masses: m 1 and m 3) from an ion beam 2. The ion beam may be generated using any ionization method known in the art. The unit is based on the time of flight (TOF) measurement principle. The ions of the ion beam 2 are separated along their flight path F on a predetermined length of the flight path d with respect to their mass m 1 to m 3 or mass to charge ratio. Thus, different ions m 1 to m 3 impinge on the ion optical system 4, which is arranged at the end of the flight path d, at different points in time. The ions m 1 to m 3 thus require different times of flight t 1 to t 3 in order to travel along the flight path d.
The ion optics 4 are used to deflect selected ions m 1 and m 3 from the flight path F of the ion beam 2. For this purpose, the apparatus 1 is designed to control the ion optical system 4 in accordance with the flight times t 1 and t 3 of the selected ions m 1 and m 3 along the flight path d.
The undeflected ions m 2 of the ion beam 2 (which for the simplified example shown here is only the ions m 2; typically, a plurality of different ions m x to m y are not deflected from the flight path F) finally impinge on the detector unit 5, which is also any detector known in the art. For the embodiment according to fig. 5, the detector unit 5 is part of the device 1. However, a separate detector unit 5 is by no means absolutely necessary for the device 1 according to the invention. Instead, existing detector units of mass spectrometers can also be used.
In the example shown here, the device 1 further comprises a calculation unit 6 and a control unit 7, which are arranged here together by way of example. Various possibilities are conceivable within the scope of the invention in this regard, and the invention is in no way limited to the variants shown here. Rather, a number of other variations are contemplated, all of which fall within the scope of the invention. For example, the computing unit 6 may also be part of the detector unit 5.
By means of the calculation unit, the time of flight t 1 to t 3, the mass m 1 to m 3, the charge, the mass-to-charge ratio and/or the intensity of the ions contained in the ion beam 2 can be determined. The control unit 7 is then arranged to control the ion optical system 4 in dependence on the flight times t 1 and t 3 of the selected ions m 1 and m 3 along the flight path d. In the present case, the ion optical system 4 is switched on, for example, at times t 1 and t 3, respectively, so that the selected ions m 1 and m 3 are deflected from the flight path F. For example, to deflect selected ions m 1 and m 3, the ion optics include a brabender nielsen gate.
According to the invention, at least one ion m 1 or m 3 is filtered in each case; in addition to each of the selected ions m 1 and m 3, it is also possible to deflect the selected range as a whole with the selected ions from the flight path F. These ranges are, for example, selected ranges for mass, charge, mass-to-charge ratio, and/or intensity for each selected ion. All ions whose mass, charge, mass-to-charge ratio and/or intensity fall within the respective selected ranges are then filtered out.
The invention is also not limited to determining the selected ions m 1 and m 3 based on the spectra recorded by the detector unit 5. For example, the selected ions m 1 and m 3 may also be selected based on a specified list. In this respect, a number of other possibilities are also conceivable, all falling within the scope of the invention.
Fig. 2 shows another embodiment of the device 1 according to the invention. In addition to the embodiment according to fig. 1, the apparatus 1 according to fig. 2 comprises an ion trap 8, which ion trap 8 is arranged between the ion optical system 4 and the detector unit 5. Therefore, the elements explained in connection with fig. 1 will not be discussed here.
In the ion trap 8, the predetermined ions m 2 are accumulated or consumed before they impinge on the detector unit 5. Instead of the individual ions m 2 shown here, a plurality of predetermined ions or at least one predetermined range of ions can also be accumulated or consumed.
Fig. 3 shows a third embodiment of the device 1 according to the invention. Unlike the embodiment according to fig. 1, the device 1 according to fig. 3 comprises an ion optical system 9. The explained elements are also not discussed in connection with fig. 3.
Similar to ion optical system 4, ion optical system 9 is controllable. In the present case, by suitably adjusting at least the individual components, here by way of example 9a and 9c, it is achieved that the entire ion beam 2 follows the flight path F 1 and is detected in its entirety by the detector unit. At least one point in time, by further suitably adjusting at least the individual components, here by way of example 9a and 9c, it can be achieved that the ion beam 2 travels along a flight path F 2, wherein the selected ions m 1 and m 3 are deflected from their flight path F 2 before the remaining ion beam 2 reaches the detector unit 5.
The ion optical system 9 outlined herein comprises a so-called ion pusher 9a, a reflector 9b and an ion mirror 9c. In addition to the embodiments shown here, a number of other embodiments of the ion optical system 9 are possible, which have other components, a different number of components and/or other arrangements of components, and likewise fall within the scope of the invention.
For the embodiment shown, the ion optical system 9 is also controlled by the control unit 7. However, it goes without saying that the ion optical system 9 in the other embodiments may also be appropriately controlled in a different manner.
By using the ion optical system 9, it is advantageously possible by the apparatus 1 to perform a scan over the whole available mass range and to perform a scan over a predetermined sub-range or over the whole available range minus the selected ions m 1 and m 3.
Fig. 4 shows a mass spectrometer 10 with a device 1 according to the invention, which device 1 is similar to the embodiment of the device 1 according to fig. 3. The mass spectrometer 10 may be any mass spectrometer according to the prior art. The mass spectrometer comprises an ionization unit 11, an analyzer and a detector, both combined with other components of the mass spectrometer 10 indicated by reference numeral 12, by which ionization unit 11 an ion beam 2 is generated. The device 1 according to the invention is arranged between an ionization unit 11 and the remaining components of the mass spectrometer 10, which are combined by reference numeral 12. In the embodiment shown, the device 1 does not have its own detector unit 5, but uses an existing detector unit of the mass spectrometer 10. The same applies to the calculation unit 6 and the control unit 7. The latter is also a component of the mass spectrometer 10 and is combined by reference numeral 12. Control of the ion optical system 4 and the remaining components of the apparatus 1 is performed similarly to the embodiments shown in the previous figures. It should be noted that naturally, in other embodiments, there may also be a separate detector unit 5, calculation unit 6 and/or control unit 7 for the device 1.
In the case of a mass spectrometer 10 according to the invention, the device 1 can on the one hand be formed as a stand-alone unit, which can be integrated into an existing mass spectrometer 10, as in the case of fig. 4. However, the stand alone unit may also be an integral part of the mass spectrometer 10 as is the case with the exemplary embodiment shown in fig. 5. The embodiment shown in fig. 5 is a TOF mass spectrometer. In the case of such a mass spectrometer 10, the device 1 according to the invention can be integrated in a particularly simple manner.
As in the case of fig. 4, the mass spectrometer comprises an ionization cell 11. Furthermore, an optical focusing unit 13 is optionally present. The mass spectrometer 10 is also shown with ion optics 9a ', 9b ' and a cell 3' for creating an electric field to accelerate ions along a flight path of a predetermined length d. Such components substantially correspond to those in the previous figures provided with the same reference numerals but without an apostrophe. However, in the present case, such components are part of an existing mass spectrometer 10. In contrast, the device 1 does not have corresponding individual components. Instead, the detector unit 5 and the ion optical system 4 are components of the apparatus 1 according to the invention. The figure has omitted the illustration of the calculation unit 6 and the control unit 7 for simplicity. For example, the calculation unit and the control unit may be implemented according to one of the previously described embodiments. Alternatively, the apparatus 1 or mass spectrometer 10 may have other components already discussed in connection with the previous figures. For example, the ion optics may comprise an ion mirror 9c or other unit for directing and/or focusing the ion beam, or an ion trap 8 may additionally be present.
Finally, a schematic illustration of the method according to the invention is shown in fig. 6. Fig. 6a shows a complete mass spectrum over the usable range of mass to charge ratios I (m/z). The ion beam 2 contains various ions m 1 to m 6, of which only ions m 1 to m 4 can be observed in the spectrum due to the low concentration of certain ions. The concentrations and thus the intensities of ions m 5 and m 6 are so low that these ions are below the sensitivity limit d L of the mass spectrometer 10. However, since the ion m 4 is only slightly above the sensitivity limit d L of the mass spectrometer 10, it is also difficult to detect.
In order to be able to detect also low concentrations of substances, in a first step or in the course of the filtration, the ions m 1 and m 3 are selectively filtered on the basis of the method according to the invention, according to one of the described embodiments. For this purpose, the ions m 1 and m 3 are selectively deflected by the ion optical system 4 at the instants t 1 and t 3, respectively, when they impinge on the ion optical system 4. Thus, the filter pattern used comprises two filter windows.
The result of this filtering is shown in fig. 6 b. The concentrations of ions m 1 and m 3 decrease significantly and are now, in an ideal case, below the original sensitivity limit d L. On the other hand, ions m 2 and m4 can now be clearly detected simultaneously, due to the downward movement of the dynamic sensitivity range.
In order to be able to detect even lower concentrations of ions, such as ions m 5 and m 6 shown in dashed lines in fig. 6c, a further filtering process for the second ions m 2 may be performed through an additional filter window as shown in fig. 6 c. Thus, in addition to ions m 1 and m 3, ion m 2 is also selectively filtered. The result of this further filtering is the subject of fig. 6 d. Ions m 5、m2 and m 6, which were previously undetectable, can now be clearly detected. Depending on the application, a suitable filter pattern may be designed by the method according to the invention, which selectively filters predetermined ions m x or predetermined ranges (e.g. mass ranges Δm) from the ion beam 2 during one or more subsequent filtering processes.
Reference symbols
1. The device according to the invention
2. Ion beam
3. Unit for creating an electric field
4. Ion optical system
5. Detector unit
6. Calculation unit
7. Control unit
8. Ion trap
9. 9A-9c ion optical system
10. Mass spectrometer
11. Ionization unit
12. Analyzer, detector and other components of a mass spectrometer
F. F 1、F2 flight path
M 1-m6、mx ion mass
Δm predetermined mass range
T 1-t3 flight time
D flight route
M 1、m3 selected ion mass
M 2 predetermined ion mass
Predetermined filter window for F 1-F3 filter modes
Claims (13)
1. An apparatus (1) for filtering at least one selected ion (m 1、m3) from an ion beam (2), the apparatus comprising:
-a unit (3) for creating an electric field to accelerate ions of the ion beam (2) along a flight path (d) of a predetermined length, and
-An ion optical system (4), the ion optical system (4) being configured to be controllable in a time-dependent manner, the ion optical system (4) demarcating the flight path (d) in one direction, the ion optical system (4) being arranged in an end region of the flight path and being for deflecting the at least one selected ion (m 1、m3) from the flight path (d) of the ion beam (2),
An ion trap (8), the ion trap (8) being adapted to accumulate at least one predetermined ion (m 2) or a plurality of predetermined ions within at least one predetermined range, the range comprising undeflected ions of the ion beam, wherein the ion trap is arranged between the ion optical system and a detector unit configured to record a mass spectrum,
Wherein the device (1) is designed to control the ion optical system (4) as a function of a time of flight (t 1、t3) of the at least one selected ion (m 1、m3) along the flight path (d), wherein the ion optical system (4) is configured to be turned on during at least one time interval in which the at least one selected ion (m 1、m3) passes through the ion optical system (4), wherein an intensity or a number of the at least one selected ion (m 1、m3) exceeds a predetermined limit value.
2. The device (1) according to claim 1,
Wherein the detector unit (5) is designed to detect and/or determine the mass, charge, mass-to-charge ratio and/or intensity of ions (m 1 to m 3) contained in the ion beam (2).
3. The device (1) according to claim 1 or 2,
Comprising a calculation unit (6), the calculation unit (6) being designed to determine a time of flight, mass, charge, mass-to-charge ratio and/or intensity of ions (m 1 to m 3) contained in the ion beam (2).
4. The device (1) according to claim 1 or 2,
Comprises a control unit (7), the control unit (7) being designed to control the ion optical system (4) as a function of a time of flight (t 1、t3) of the selected ions (m 1、m3) along the flight path (d).
5. The device (1) according to claim 1 or 2,
Wherein the ion optical system (4) comprises at least one brabender-nielsen gate.
6. The device (1) according to claim 1,
Wherein the ion trap (8) is an orbitrap or a C-trap.
7. The device (1) according to claim 1 or 2,
Comprises a second ion optical system (9), the second ion optical system (9) being adapted to direct the ion beam (2) at least at a predetermined point in time such that the ion beam (2) passes through the apparatus (1).
8. A mass spectrometer (10) device comprising the device (1) according to any one of claims 1 to 7.
9. A method for filtering at least one selected ion (m 1、m3) from the ion beam (2), by means of an apparatus (1) according to any one of claims 1 to 7, comprising the following method steps:
Accelerating ions of the ion beam (2) along a flight path (d) of a predetermined length,
-Deflecting, by means of the ion optical system (4), the at least one selected ion (m 1、m3) from a flight path (F) of the ion beam (2) in accordance with a time of flight (t 1、t3) of the at least one selected ion (m 1、m3) along the flight path (d), wherein an intensity or a number of the at least one selected ion (m 1、m3) exceeds a predetermined limit value,
Controlling the ion optical system (4) to be configured to be turned on during at least one time interval when the at least one selected ion (m 1、m3) passes through the ion optical system (4),
-Accumulating, by the ion trap, at least one predetermined ion (m 2) within at least one predetermined range, the range comprising undeflected ions of the ion beam.
10. The method according to claim 9, wherein the method comprises,
Wherein the selected ions (m 1、m3) are determined based on at least one mass spectrum of the ion beam (2) and/or based on a mass, charge, mass-to-charge ratio and/or intensity of ions (m 1、m3) contained in the ion beam (2).
11. The method according to claim 9, wherein the method comprises,
Wherein the accumulation factor is determined.
12. The method of claim 9, wherein the step of determining the position of the substrate comprises,
Wherein at least one predetermined ion (m 2) or a plurality of predetermined ions within the predetermined range are accumulated with a predetermined accumulation factor.
13. The method of claim 9, wherein the step of determining the position of the substrate comprises,
Wherein at least one predetermined ion (m 2) or a plurality of predetermined ions within the predetermined range are consumed at a predetermined consumption factor.
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| Application Number | Priority Date | Filing Date | Title |
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| DE102018116305.3A DE102018116305B4 (en) | 2018-07-05 | 2018-07-05 | Dynamic ion filter to reduce highly abundant ions |
| DE102018116305.3 | 2018-07-05 | ||
| PCT/EP2019/065426 WO2020007580A1 (en) | 2018-07-05 | 2019-06-13 | Dynamic ion filter for reducing high-abundance ions |
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| CN112689884A CN112689884A (en) | 2021-04-20 |
| CN112689884B true CN112689884B (en) | 2024-05-24 |
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| US (1) | US11488818B2 (en) |
| EP (1) | EP3818555A1 (en) |
| CN (1) | CN112689884B (en) |
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| DE102007045361B4 (en) | 2007-09-22 | 2012-04-12 | Helmholtz Zentrum München Deutsches Forschungszentrum Für Gesundheit Und Umwelt (Gmbh) | Method and device for the detection of organic trace constituents on surfaces |
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| US10304674B2 (en) * | 2014-08-19 | 2019-05-28 | Micromass Uk Limited | Time of flight mass spectrometer |
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| US6534764B1 (en) * | 1999-06-11 | 2003-03-18 | Perseptive Biosystems | Tandem time-of-flight mass spectrometer with damping in collision cell and method for use |
| JP2007335368A (en) * | 2006-06-19 | 2007-12-27 | Jeol Ltd | Time-of-flight mass spectrograph method and device |
| CN103038858A (en) * | 2010-07-30 | 2013-04-10 | 约恩-托福技术有限公司 | Method and a mass spectrometer and uses thereof for detecting ions or subsequently-ionised neutral particles from samples |
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| Publication number | Publication date |
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| EP3818555A1 (en) | 2021-05-12 |
| DE102018116305A1 (en) | 2020-01-09 |
| CN112689884A (en) | 2021-04-20 |
| DE102018116305B4 (en) | 2023-05-25 |
| WO2020007580A1 (en) | 2020-01-09 |
| US20210287895A1 (en) | 2021-09-16 |
| US11488818B2 (en) | 2022-11-01 |
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